2024
The human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity
Marin-Lopez A, Huck J, Esterly A, Azcutia V, Rosen C, Garcia-Milian R, Sefik E, Vidal-Pedrola G, Raduwan H, Chen T, Arora G, Halene S, Shaw A, Palm N, Flavell R, Parkos C, Thangamani S, Ring A, Fikrig E. The human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity. Science Immunology 2024, 9: eadk9872. PMID: 39121194, DOI: 10.1126/sciimmunol.adk9872.Peer-Reviewed Original ResearchConceptsSuppress antiviral responsesArthropod proteinsPathogen replicationAntiviral responseProtein AVertebrate hostsMosquito salivary proteinsUp-regulatedBlood feedingHuman macrophagesPleomorphic effectsSkin infectionsZika virus disseminationInhibit proinflammatory responsesSalivary proteinsProteinNatural ligandWhite blood cellsHuman skin explantsProinflammatory responseMosquito salivaVirus disseminationHuman CD47Salivary factorsArbovirus infection
2021
Aedes aegypti SNAP and a calcium transporter ATPase influence dengue virus dissemination
Marin-Lopez A, Jiang J, Wang Y, Cao Y, MacNeil T, Hastings AK, Fikrig E. Aedes aegypti SNAP and a calcium transporter ATPase influence dengue virus dissemination. PLOS Neglected Tropical Diseases 2021, 15: e0009442. PMID: 34115766, PMCID: PMC8195420, DOI: 10.1371/journal.pntd.0009442.Peer-Reviewed Original ResearchConceptsSalivary gland proteinsSuccessful viral transmissionNew mammalian hostDengue virusWild habitatsHabitat expansionGland proteinsA. aegypti vectorMammalian hostsUbiquitous expressionDENV infectionGene expressionMosquito midgutProtein componentsATPase proteinVector proteinProteinSalivary glandsBlood mealViral cycleAedes aegypti mosquitoesSusceptible hostsAedes aegyptiMosquitoesHostAgBR1 and NeSt1 antisera protect mice from Aedes aegypti-borne Zika infection
Marin-Lopez A, Wang Y, Jiang J, Ledizet M, Fikrig E. AgBR1 and NeSt1 antisera protect mice from Aedes aegypti-borne Zika infection. Vaccine 2021, 39: 1675-1679. PMID: 33622591, PMCID: PMC7990057, DOI: 10.1016/j.vaccine.2021.01.072.Peer-Reviewed Original ResearchConceptsMosquito saliva proteinsPassive immunizationZIKV infectionEarly host responseDiverse clinical symptomsViral burdenSaliva proteinsClinical symptomsVaccine strategiesZika infectionHost responseModel antigenInfectionPartial protectionMiceImmunizationZIKVAntiserumIndividual antiseraAgBR1ViremiaSymptomsAntigenBloodAntibodies
2020
TRiC/CCT Complex, a Binding Partner of NS1 Protein, Supports the Replication of Zika Virus in Both Mammalians and Mosquitoes
Wang Y, Uraki R, Hwang J, Fikrig E. TRiC/CCT Complex, a Binding Partner of NS1 Protein, Supports the Replication of Zika Virus in Both Mammalians and Mosquitoes. Viruses 2020, 12: 519. PMID: 32397176, PMCID: PMC7290343, DOI: 10.3390/v12050519.Peer-Reviewed Original ResearchConceptsZika virusZIKV replicationZIKV NS1 proteinGuillain-Barré syndromeNS1 proteinTRiC/CCT complexPromising therapeutic targetZIKV infectionCongenital microcephalySpecific treatmentTherapeutic targetHost factorsVirusMosquitoesSyndromeVaccineSymptomsInfectionMicrocephalyProteinReplicationImportant role
2019
Aedes aegypti NeSt1 Protein Enhances Zika Virus Pathogenesis by Activating Neutrophils
Hastings AK, Uraki R, Gaitsch H, Dhaliwal K, Stanley S, Sproch H, Williamson E, MacNeil T, Marin-Lopez A, Hwang J, Wang Y, Grover JR, Fikrig E. Aedes aegypti NeSt1 Protein Enhances Zika Virus Pathogenesis by Activating Neutrophils. Journal Of Virology 2019, 93: 10.1128/jvi.00395-19. PMID: 30971475, PMCID: PMC6580965, DOI: 10.1128/jvi.00395-19.Peer-Reviewed Original ResearchConceptsVirus infectionBite siteMosquito salivaImmune cellsZika virusLocal immune environmentMosquito bite siteZika virus pathogenesisEarly viral replicationZika virus infectionFactor 1Pathogenesis of flavivirusesVirus-infected mosquitoesVirus-induced pathogenesisCXCL2 expressionImmune environmentPassive immunizationZIKV pathogenesisImmune microenvironmentAntibody responseZIKV replicationVirus pathogenesisMosquito bitesPrimary mouse neutrophilsImmune systemAedes aegypti AgBR1 antibodies modulate early Zika virus infection of mice
Uraki R, Hastings AK, Marin-Lopez A, Sumida T, Takahashi T, Grover JR, Iwasaki A, Hafler DA, Montgomery RR, Fikrig E. Aedes aegypti AgBR1 antibodies modulate early Zika virus infection of mice. Nature Microbiology 2019, 4: 948-955. PMID: 30858571, PMCID: PMC6533137, DOI: 10.1038/s41564-019-0385-x.Peer-Reviewed Original ResearchConceptsZika virus infectionVirus infectionZika virusAegypti salivary proteinsGuillain-Barre syndromeEarly inflammatory responseSkin of micePrevention of mosquitoInflammatory responseAedes aegypti mosquitoesTherapeutic measuresSalivary factorsSalivary proteinsMosquito-borneInfectionMiceSubstantial mortalityRecent epidemicProtein 1Aegypti mosquitoesAntigenic proteinsVirusAntibodiesMosquitoesAntiserum
2018
A potent prolyl tRNA synthetase inhibitor antagonizes Chikungunya and Dengue viruses
Hwang J, Jiang A, Fikrig E. A potent prolyl tRNA synthetase inhibitor antagonizes Chikungunya and Dengue viruses. Antiviral Research 2018, 161: 163-168. PMID: 30521835, PMCID: PMC6345585, DOI: 10.1016/j.antiviral.2018.11.017.Peer-Reviewed Original ResearchConceptsDengue virusSignificant morbiditySafe vaccineSynthetase inhibitionEndemic areasSynthetase inhibitorFlavivirus genusMosquito-bornePotent antagonistHost factorsGroup of pathogensVirusMultiple virusesChikungunyaHematophagous arthropod vectorsAedes sppArthropod vectorsEpidemic pathogensAdditional approachesMorbidityPathogensVaccineAntagonistMortalityHuman populationAltered vector competence in an experimental mosquito-mouse transmission model of Zika infection
Uraki R, Hastings AK, Gloria-Soria A, Powell JR, Fikrig E. Altered vector competence in an experimental mosquito-mouse transmission model of Zika infection. PLOS Neglected Tropical Diseases 2018, 12: e0006350. PMID: 29505571, PMCID: PMC5854422, DOI: 10.1371/journal.pntd.0006350.Peer-Reviewed Original ResearchConceptsZIKV transmissionZika virus infectionNatural transmission routeInfected miceZIKV infectionZika infectionTesting vaccinesVirus infectionIntrathoracic injectionAnimal modelsZIKVInfectionMiceTransmission routesBlood mealVector competenceVector competencyMosquitoesTransmission modelVertebrate hostsMosquito modelPathogenesisVaccine
2017
Zika Virus and Sexual Transmission: A New Route of Transmission for Mosquito-borne Flaviviruses.
Hastings AK, Fikrig E. Zika Virus and Sexual Transmission: A New Route of Transmission for Mosquito-borne Flaviviruses. The Yale Journal Of Biology And Medicine 2017, 90: 325-330. PMID: 28656018, PMCID: PMC5482308.Peer-Reviewed Original ResearchConceptsSexual transmissionZika virusWorld Health OrganizationWest Nile virusAcute onset paralysisUnprotected sexual contactRoutes of transmissionNew global epidemicSevere birth defectsBody achesMild feverAnimal modelsInfected mosquitoesVaginal secretionsViral infectionMain mosquito vectorGlobal epidemicFlaviviridae familyImportant human pathogenSexual contactDisease controlHealth OrganizationZika transmissionNile virusBirth defects
2016
Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection
Conway MJ, Londono-Renteria B, Troupin A, Watson AM, Klimstra WB, Fikrig E, Colpitts TM. Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection. PLOS Neglected Tropical Diseases 2016, 10: e0004941. PMID: 27632170, PMCID: PMC5025043, DOI: 10.1371/journal.pntd.0004941.Peer-Reviewed Original ResearchConceptsSalivary gland extractsDengue virus infectionD7 proteinDengue virus type 1Virus type 1DENV envelope proteinAegypti salivaLymph nodesDENV infectionDENV virionsVirus infectionRelevant arbovirusesType 1InfectionHost skinBlood feedingEnvelope proteinNovel roleBinding assaysSalivaAedes aegyptiGland extractsPrimary vectorHPLC fractionsFeedingA novel mosquito ubiquitin targets viral envelope protein for degradation and reduces virion production during dengue virus infection
Troupin A, Londono-Renteria B, Conway MJ, Cloherty E, Jameson S, Higgs S, Vanlandingham DL, Fikrig E, Colpitts TM. A novel mosquito ubiquitin targets viral envelope protein for degradation and reduces virion production during dengue virus infection. Biochimica Et Biophysica Acta 2016, 1860: 1898-1909. PMID: 27241849, PMCID: PMC4949077, DOI: 10.1016/j.bbagen.2016.05.033.Peer-Reviewed Original ResearchConceptsProtein degradationUbiquitin proteinGene expressionProtein expression constructsSite-directed mutagenesisViral protein degradationInnate immune signalingDengue virusProteasomal degradationProtein interactionsExpression constructsMosquito cellsSignificant human diseaseMicroarray analysisImmune signalingViral envelope proteinsVirus infectionHuman diseasesBlood feedingAmino acidsProteinMultiple functionsQRT-PCRVirion productionAntiviral function
2015
Dengue Virus Infection of Aedes aegypti Requires a Putative Cysteine Rich Venom Protein
Londono-Renteria B, Troupin A, Conway MJ, Vesely D, Ledizet M, Roundy CM, Cloherty E, Jameson S, Vanlandingham D, Higgs S, Fikrig E, Colpitts TM. Dengue Virus Infection of Aedes aegypti Requires a Putative Cysteine Rich Venom Protein. PLOS Pathogens 2015, 11: e1005202. PMID: 26491875, PMCID: PMC4619585, DOI: 10.1371/journal.ppat.1005202.Peer-Reviewed Original ResearchConceptsDENV infectionVirus infectionDengue virusCysteine-rich venom proteinsSpecific antiviral therapyDengue virus infectionMosquito-borne flavivirusAedes aegypti cellsAntiviral therapyFlavivirus infectionMultiple flavivirusesTherapeutic measuresNew treatmentsAedes aegyptiInfectionGene targetsSerious human diseasesAegypti cellsMosquito vectorsVaccineVenom proteinsFlavivirusesHuman diseasesMosquitoesAntiserum inhibits
2011
Alterations in the Aedes aegypti Transcriptome during Infection with West Nile, Dengue and Yellow Fever Viruses
Colpitts TM, Cox J, Vanlandingham DL, Feitosa FM, Cheng G, Kurscheid S, Wang P, Krishnan MN, Higgs S, Fikrig E. Alterations in the Aedes aegypti Transcriptome during Infection with West Nile, Dengue and Yellow Fever Viruses. PLOS Pathogens 2011, 7: e1002189. PMID: 21909258, PMCID: PMC3164632, DOI: 10.1371/journal.ppat.1002189.Peer-Reviewed Original ResearchConceptsGene expressionDiverse cellular processesPupal cuticle proteinsExpression of genesMosquito gene expressionYellow fever virusFlaviviral infectionsMosquito genesCuticle proteinsCellular processesBioinformatics analysisMosquito cellsExpression profilesMicroarray analysisDDR genesMetabolic processesHuman diseasesGenesTranscriptomic signaturesWest NileFever virusPeptidase activityWNV envelope proteinTranscriptomeAedes aegypti mosquitoesAn In Vivo Transfection Approach Elucidates a Role for Aedes aegypti Thioester-Containing Proteins in Flaviviral Infection
Cheng G, Liu L, Wang P, Zhang Y, Zhao YO, Colpitts TM, Feitosa F, Anderson JF, Fikrig E. An In Vivo Transfection Approach Elucidates a Role for Aedes aegypti Thioester-Containing Proteins in Flaviviral Infection. PLOS ONE 2011, 6: e22786. PMID: 21818390, PMCID: PMC3144946, DOI: 10.1371/journal.pone.0022786.Peer-Reviewed Original Research
2010
A C-Type Lectin Collaborates with a CD45 Phosphatase Homolog to Facilitate West Nile Virus Infection of Mosquitoes
Cheng G, Cox J, Wang P, Krishnan MN, Dai J, Qian F, Anderson JF, Fikrig E. A C-Type Lectin Collaborates with a CD45 Phosphatase Homolog to Facilitate West Nile Virus Infection of Mosquitoes. Cell 2010, 142: 714-725. PMID: 20797779, PMCID: PMC2954371, DOI: 10.1016/j.cell.2010.07.038.Peer-Reviewed Original ResearchConceptsWest Nile virusWNV infectionWest Nile virus infectionArthropod-borne flavivirusBlood-feeding processVirus infectionHuman CD45Viral disseminationC-type lectinInfectionViral entryViral attachmentMosquito homologCalcium-dependent mannerNile virusMolecular understandingVivo experimentsSame pathwayNatural vector